Surgery professor Dr. Lawrence Rosenberg

PHOTO: OWEN EGAN

Can diabetes be defeated?

SYLVAIN COMEAU | An ongoing research project may hold out hope for a cure for diabetes, according to surgery professor Dr. Lawrence Rosenberg.

Rosenberg, along with McGill and U.S. collaborators, discovered and cloned a gene, called the INGAP (Islet neogenesis associated protein) gene, which addresses one of the underlying causes of certain types of diabetes.

"This is a gene found in the pancreas which produces a protein that appears to be responsible for the formation of new insulin-producing beta-cells."

Animal studies have been more than promising.

"We've been able to reverse -- cure -- the disease in diabetic animals by giving them an injection of this protein. We've been able to double the number of islets. We've also seen an increase in insulin-producing cells in normal animals, and none of the animals have suffered any side effects."

Rosenberg cautions, however, that the lab breakthrough won't necessarily translate into a cure for humans.

"Often, something will work perfectly in the lab, but when you try it on people, you get unexpected complications, such as side effects."

He is also quick to point out that drugs emerging from this discovery, if any, will take several years to materialize.

"We will still have to take the drug through a regulatory process, to get it approved by the U.S. Food and Drug Administration, which will probably take five years. We may be able to get it into clinical (human) trials in 18 months, but getting it to market could mean another three to five years."

Rosenberg, the director of McGill's Division of Surgical Research, says that the gene is not an abnormal mutation; it is a normal gene, which may be defective in diabetic individuals.

"The INGAP protein is probably important in normal pancreatic development. We're still looking at why the INGAP gene would not automatically prevent the onset of diabetes. One possibility is that it requires a stimulus to be turned on, which is true of a lot of genes. Another is that the INGAP protein itself could be altered. Part of the human trials could be to examine the gene and the protein in diabetic patients."

The discovery could yield two different kinds of drugs.

"We may be able to administer the INGAP protein as a drug, without dealing with the gene. Alternatively, we also could come up with a strategy for turning on the gene, without having to administer the protein."

In addition, the animal models suggest that patients would only have to have one course of treatment, in contrast to most other drugs designed for chronic diseases.

"So far, it looks like the animals in our lab tests don't have to continue taking it. Once you've repopulated the pancreas with new insulin producing cells, [the cells] don't disappear."

However, even if an effective drug is developed, Rosenberg is not sure that it would be effective in all types of diabetes.

"There are two types of diabetes; there is Type I, in which people lack insulin, and Type II, in which people are resistant to the effects of insulin, because they lack a receptor on the appropriate cell to recognize it. INGAP is more likely to help the Type I diabetics, who don't have any insulin because their immune system mistakenly wiped it out."

Thus, for Type I diabetics, whose disease is based on an autoimmune dysfunction, the drug would have to be combined with immune therapy.

"Their own bodies destroyed their insulin producing cells in childhood, and the INGAP protein could replace an insulin producing cell mass. The problem is that their immune systems may destroy the cells again. So our therapy would have to be combined with a treatment which suppresses that aspect of their immune response. We are conducting an animal study to test this strategy.

"We're very excited about this," Rosenberg adds, "because of the animal model results. As far as I know, no one else has discovered anything which induces the formation of new islets. Our molecule seems to be very potent, even compared to ones already in clinical trials."

Rosenberg's collaborators are pathology professor Dr. William Duguid, and Dr. Arthur Vinik of Eastern Virginia Medical School. Eli Lilly, which had previously licensed the team's work, has let the license expire as it focuses its attention on other shorter-term projects. The company had no qualms with the strength of the team's scientific approach, though and Rosenberg believes he is close to securing an agreement with another corporate partner, to license the technology and bring it to market.